The aim of these studies is to measure with radionuclide techniques the change in the extent of irreversibly damaged myocardium with time during the early phase of acute myocardial infarction. In previous studies completed by the applicant, detection of the acute infarct was possible as early as four hours after onset of symptoms. Biological constraints preclude the use of currently available radiotracers for measuring infarct size at this early time after infarction. Using structure:activity relationships (defined in previous studies by this investigator), we propose to synthesize radiopharmaceuticals which sequester avidly in irreversibly damaged myocardium. These radiotracers will be tested in a canine model of acute myocardial infarction to assess the concentration in the infarct relative to irreversibly ischemic and normal myocardium soon after coronary occlusion. The most promising of these tracers will be studied in man to 1) define the time course of the extent of irreversible injury after onset of infarction and 2) assess the efficacy of on-line therapy (such as hyaluronidase and propranolol) aimed at limiting the extent of infarction. These studies should help to provide objective criteria to evaluate the possibility of salvaging reversibly ischemic myocardium using pharmaceutical, mechanical or surgical interventions during the early phase of acute myocardial infarction.